Using approved LOPD combination therapy at home is safe, study finds
Reactions with Pombiliti plus Opfolda similar in clinic or home administration
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Home-based administration of Pombiliti plus Opfolda (cipaglucosidase alfa/miglustat), an approved combination therapy for late-onset Pompe disease (LOPD), appears to be safe for certain adults with LOPD, according to a pooled analysis from three clinical trials.
In reviewing more than 9,000 treatment doses given to about 150 patients worldwide — almost one-quarter of which were administered at home — the researchers found that the rate of infusion-related reactions was similar whether the treatment was administered by a healthcare professional at home or in the clinic.
Safe use of the combination therapy at home for LOPD patients, for whom symptoms start after age 1 and through adulthood, is dependent on several factors, the researchers noted. Among them is close proximity to emergency care facilities should treatment be needed for any reactions that occur.
Overall, these results show that “eligible patients may be able to safely receive infusions at home with a low risk of infusion-associated reactions,” the researchers wrote. “This could make [Pombiliti plus Opfolda] treatment more comfortable and convenient, and reduce the burden of traveling to a healthcare facility for treatment.”
The study, “Safety of home administration of cipaglucosidase alfa plus miglustat in late-onset Pompe disease: results from multiple clinical trials,” was published in the journal Therapeutic Advances in Rare Disease. The work was funded by the therapy’s developer, Amicus Therapeutics.
Pompe disease is caused by mutations that disrupt the production or function of acid alpha-glucosidase (GAA), an enzyme that breaks down glycogen, a complex sugar molecule. As a result, glycogen accumulates inside cells, particularly muscle and nerve cells, leading to muscle weakness and other disease symptoms.
Combination therapy given both orally and by infusion
Pombiliti plus Opfolda, approved in the U.S. and elsewhere for adults with LOPD, is designed to enhance patients’ walking ability and improve or stabilize their respiratory function. Pombiliti, delivered via intravenous, or into-the-vein, infusions, is an enzyme replacement therapy (ERT) that provides patients with a version of the GAA enzyme. Opfolda is an oral therapy that helps stabilize that enzyme, increasing the amount of it that reaches muscle cells.
The combo treatment was shown in clinical trials to have long-term benefits for people with LOPD.
Pombiliti infusions are administered by a trained healthcare provider, usually every two weeks. This is often done at a healthcare clinic, but in some areas, infusions can be given at home.
Studies in Pompe disease and related conditions have shown that patients reported increased treatment satisfaction and quality of life after transitioning to ERT home administration.
To learn more about this option, researchers from the U.S. and Europe — including seven scientists from Amicus, all in New Jersey — analyzed the safety of Pombiliti plus Opfolda administered at home. The team used pooled data from three clinical studies: the Phase 1/2 ATB200-02 trial (NCT02675465), the Phase 3 PROPEL study (NCT03729362), and the Phase 3 PROPEL open-label extension (NCT04138277).
A total of 151 LOPD patients from 22 countries, with a mean age at diagnosis of about 40 years, received the combination therapy. Slightly more than half were women. All were eligible to receive home-based treatment from a trained nurse if earlier infusions were well tolerated, local regulations permitted the medication to be given outside of a hospital, and home treatment was, overall, feasible in their individual situation.
Of 9,185 treatment doses, 2,024 (22.0%) were administered at home. Overall, 43% of patients received infusions both at home (at least one infusion) and in the clinic, while 57% only received clinic-based infusions. Most participants (78%) had previously received ERT.
Risk of infusion reactions tied to Pombiliti
A particular safety concern with Pombiliti is the risk of severe infusion-associated reactions, or IARs. The data showed that participants who received treatment at home and those treated in the clinic had similar rates of IARs (1.3% vs. 1.8%). The most common reaction at home was fever (6.2%), while headache (10.8%) and fever (6.2%) were most common in the clinic.
Two patients who had home-based treatments, and had not been previously treated with ERT before the trial, experienced a serious IAR. One patient experienced a serious fever at home, but continued receiving home-based treatment. Another patient experienced presyncope — the sensation of being about to lose consciousness, without actually passing out — in the clinic before starting home infusion.
Overall, the results of this … analysis of safety data pooled from three clinical trials support the safety of home-based administration of [Pombiliti plus Opfolda] in … adults with LOPD.
There were two accidental medication overdoses in these studies: one at home and one in the clinic. Neither patient experienced any adverse outcomes associated with the overdose, the researchers noted.
“Overall, the results of this … analysis of safety data pooled from three clinical trials support the safety of home-based administration of [Pombiliti plus Opfolda] in ERT-experienced and ERT-naïve adults with LOPD,” the researchers wrote.
The team noted that the safety and feasibility of home administration depend on several factors, including proper patient selection and proximity to emergency care facilities, should immediate care be needed. The availability of appropriately trained healthcare professionals was also cited as key to successful home use.
